The proposed Program Project in cellular and immunological bases of pulmonary diseases is composed of a group of senior investigators representing several different disciplines (anatomy, physiology, pharmacology, microbiology, immunology, pathology, computer sciences, pediatrics and medicine) with related interests, and who, working individually and in collaboration, are interested in elucidating the molecular, biochemical and immunological mechanisms of pulmonary diseases in the human. The primary objective is to study how alterations of the processing of foreignness by the lung may result in initiation or exacerbation of pulmonary disease processes in the human. By an understanding of these mechanisms, it may be possible to provide a more rational approach to the diagnosis, treatment and ultimate prevention of these pulmonary diseases. It is our intent to accomplish this primary objective by providing a research environment favorable for the interaction and collaboration of both basic scientists and clinical investigators in order to facilitate the correlation of basic laboratory and clinical endeavors. The approach to be employed in these studies will range from the utilization of isolated alveolar macrophages to the study of the patient with pulmonary disease. The mechanisms by which the alveolar macrophage protects the lungs in both the healthy and disease states will be investigated in order to provide clues as to how these alterations may lead to disease. This will be accomplished by a study of alterations which occur both naturally and experimentally in situ as well as in vitro. The focus of previous studies has been directed towards elucidation of factors in the pathogenesis of pulmonary disease and has centered primarily on the adult with chronic end-stage disease. Relatively little effort has been directed toward the study of antecedents of adult disease in the pediatric age-group. In the present program, both clinical and basic science projects will include not only pulmonary diseases of the adult patient but also the generally neglected area of pulmonary disease in infancy and childhood.